This project will try to define the biochemical events which follow the application of a physiological stress on the heart resulting in cardiac enlargment and hypertrophy. We hope to elucidate some of the basic mechanisms involved in the development of cardiac hypertrophy in patients with valvular and ischemic heart disease. The major objectives are 1.) to elucidate the mechanisms which control the process of protein and nucleic acid synthesis in a differentiated tissue such as the heart of higher organisms 2.) to study the mechanisms of assembly and control of replication of mitochondria in differentiated tissue. In this project we plan to use several model systems with the following specific aims in mind: 1. To determine whether the increased protein synthesis seen in cardiac hypertrophy is secondary to an increased number of ribosomes and to increased messenger activity. Changes in polysome pattern and in the distribution of free and bound ribosomes early after aortic banding in the rat will be studied. 2. To determine the effect of a stimulus for growth on the turnover of muscle proteins. 3. To study the mechanism of increase in nuclear RNA polymerase after the initiation of cardiac hypertrophy. 4. To evaluate the possible existence of amplification of genes coding for ribosomal RNA following a growth stimulus. 5. To measure the time course of the changes in mitochondrial enzyme activity, cytochrome and phospholipid content after the initiation of cardiac hypertrophy. 6. To determine the effect of the growth stimulus on the turnover of various mitochondrial components DNA, phospholipid and protein; also to compare the turnover rates of inner and outer mitochondrial membranes.